RESUMO
McArdle disease is a metabolic myopathy that can may lead to severe perioperative problems. A case is reported of a woman with a history of McArdle disease, who was scheduled for a mastectomy. An understanding of the physiology and pathology, and the application of appropriate preventive measures can avoid complications. A overview of the complications and the management are described.
Assuntos
Anestesia Geral/métodos , Doença de Depósito de Glicogênio Tipo V/fisiopatologia , Complicações Intraoperatórias/prevenção & controle , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Anestesia Geral/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Carcinoma/cirurgia , Feminino , Glucose/administração & dosagem , Doença de Depósito de Glicogênio Tipo V/complicações , Humanos , Hipoglicemia/etiologia , Hipoglicemia/prevenção & controle , Hipotermia/prevenção & controle , Hipertermia Maligna/etiologia , Hipertermia Maligna/prevenção & controle , Mastectomia Simples , Pessoa de Meia-Idade , Mioglobinúria/etiologia , Mioglobinúria/prevenção & controleRESUMO
Myoglobinuric acute renal failure (ARF) is a uremic syndrome caused by traumatic or non-traumatic skeletal muscle breakdown and intracellular elements that are released into the bloodstream. We hypothesized that hyperbaric oxygen (HBO) therapy could be beneficial in the treatment of myoglobinuric ARF caused by rhabdomyolysis. A total of 32 rats were used in the study. The rats were divided into four groups: control, control+hyperbaric oxygen (control+HBO), ARF, and ARF+hyperbaric oxygen (ARF+HBO). Glycerol (8 ml/kg) was injected into the hind legs of each of the rats in ARF and ARF+HBO groups. 2.5 atmospheric absolute HBO was applied to the rats in the control+HBO and ARF+HBO groups for 90 min on two consecutive days. Plasma urea, creatinine, sodium, potassium, calcium, aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, creatinine kinase and urine creatinine and sodium were examined. Creatinine clearance and fractional sodium excretion could then be calculated. Superoxide dismutase, catalase, glutathione and malondialdehyde (MDA) levels were assessed in renal tissue. Tissue samples were evaluated by Hematoxylin-eosin, PCNA and TUNEL staining histopathologically. MDA levels were found to be significantly decreased whereas SOD and CAT were twofold higher in the ARF+HBO group compared to the ARF group. Renal function tests were ameliorated by HBO therapy. Semiquantitative evaluation of histopathological findings indicated that necrosis and cast formation was decreased by HBO therapy and TUNEL staining showed that apoptosis was inhibited. PCNA staining showed that HBO therapy did not increase regeneration. Ultimately, we conclude that, in accordance with our hypothesis, HBO could be beneficial in the treatment of myoglobinuric ARF.
Assuntos
Injúria Renal Aguda/prevenção & controle , Oxigenoterapia Hiperbárica , Mioglobinúria/prevenção & controle , Oxigênio/uso terapêutico , Rabdomiólise/prevenção & controle , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Animais , Catalase/metabolismo , Creatinina/metabolismo , Glutationa/metabolismo , Glicerol/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Peroxidação de Lipídeos , Masculino , Malondialdeído/metabolismo , Mioglobinúria/induzido quimicamente , Mioglobinúria/metabolismo , Oxirredução , Ratos , Ratos Sprague-Dawley , Rabdomiólise/induzido quimicamente , Rabdomiólise/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Suxamethonium is a drug that promotes very strong views both for and against its use in the context of pediatric anesthesia. As such, the continuing debate is an excellent topic for a 'Pro-Con' debate. Despite ongoing efforts by drug companies, the popular view still remains that there is no single neuromuscular blocking drug that can match suxamethonium in terms of speed of onset of neuromuscular block and return of neuromuscular control. However, with this drug the balance of benefit vs risk and side effects are pivotal. Suxamethonium has significant adverse effects, some of which can be life threatening. This is particularly relevant for pediatric anesthesia because the spectrum of childhood diseases may expose susceptible individuals to an increased likelihood of adverse events compared with adults. Additionally, the concerns related to airway control in the infant may encourage the occasional pediatric anesthetist to use the drug in preference to slower onset/offset drugs. In the current environment of drug research, surveillance and licensing, it is debatable whether this drug would achieve the central place it still has in pediatric anesthesia. The arguments for and against its use are set out below by our two international experts, Marcin Rawicz from Poland and Barbara Brandom from USA. This will allow the reader an objective evaluation with which to make an informed choice about the use of suxamethonium in their practice.
Assuntos
Anestesia/métodos , Hipertermia Maligna/complicações , Doenças Musculares/complicações , Fármacos Neuromusculares Despolarizantes/efeitos adversos , Succinilcolina/efeitos adversos , Criança , Humanos , Hiperpotassemia/induzido quimicamente , Hipertermia Maligna/etiologia , Hipertermia Maligna/fisiopatologia , Hipertermia Maligna/prevenção & controle , Músculo Masseter/efeitos dos fármacos , Doenças Musculares/fisiopatologia , Mioglobinúria/fisiopatologia , Mioglobinúria/prevenção & controle , Fármacos Neuromusculares Despolarizantes/farmacologia , Potássio/metabolismo , Succinilcolina/farmacologiaRESUMO
During times of war and natural disasters, rhabdomyolysis-induced myoglobinuric acute renal failure (ARF) can assume epidemic proportions. Free radicals play an important role in the pathogenesis of myoglobinuric ARF. Vitamin C is a major antioxidant, scavenging free radicals. We have not found any studies on the effect of vitamin C on myoglobinuric ARF. Thus, we aimed to investigate the effects of vitamin C on the myoglobinuric ARF formed by glycerol in rats. Three groups of rats were employed in this study. Group 1 served as control, group 2 was given 50% glycerol (10 mL/kg, i.m.), and group 3 was given glycerol plus vitamin C (20 mg/kg, i.p. for four days). Ninety-six hours after glycerol injections, blood samples and kidney tissues were taken from the anesthetized rats. Urea and creatinine levels in plasma; N-acetyl-beta-D-glucosaminidase activity in urine; malondialdehyde levels, superoxide dismutase and catalase enzyme activity in kidney tissue were determined. Histopathological changes and iron accumulation in the kidney tissue were evaluated. In this study, glycerol administration led to marked renal oxidative stress and severe renal functional and morphological deterioration. The treatment of animals with vitamin C partially corrected the renal dysfunction and morphological impairment. In this respect, vitamin C appears to be a promising candidate for the prevention of rhabdomyolysis-induced ARF. Higher dosages of vitamin C than in 20 mg/kg may be beneficial for better functional and morphological recovery in this model ARF.
Assuntos
Injúria Renal Aguda/prevenção & controle , Ácido Ascórbico/administração & dosagem , Mioglobinúria/prevenção & controle , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Glicerol , Imuno-Histoquímica , Testes de Função Renal , Necrose Tubular Aguda/induzido quimicamente , Necrose Tubular Aguda/patologia , Necrose Tubular Aguda/prevenção & controle , Masculino , Malondialdeído/metabolismo , Mioglobinúria/induzido quimicamente , Mioglobinúria/patologia , Probabilidade , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Valores de Referência , Rabdomiólise/induzido quimicamente , Rabdomiólise/patologia , Rabdomiólise/prevenção & controle , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
Generation of reactive oxygen species significantly contribute to the pathogenesis of renal injury induced by myoglobin release. The present study was performed to investigate the effects of dietary curcumin, a natural antioxidant isolated from plant Curcuma longa, in an experimental model of myoglobinuric acute renal failure. Rats received curcumin at an oral dose of 100mg/kg/day for 30 days. Renal injury was induced with injection of hypertonic glycerol (10 ml/kg 50% solution) in hind limb muscle with blood urea of 57.8+/-7.2 vs. 7.72+/-1.03 mmol/l and serum creatinine of 444.4+/-61.3 vs. 51.8+/-10.6 micromol/l, in glycerol-induced acute renal failure (ARF) vs. control rats, respectively. After 48 h rats were sacrificed and thiobarbituric acid reactive substance (TBARS), glutathione, carbonyl content and kidney cortex brush border peptidase activities were determined in serum, kidney and liver. Rats that received curcumin in addition to glycerol had significantly lower TBARS in serum but not in kidney and liver. Carbonyl content in kidney and liver was significantly elevated in curcumin and glycerol treated rats and improved in animals treated with curcumin and glycerol together. The activities of kidney cortex enzymes, aminopeptidase N, angiotensinase A and dipeptidyl peptidase IV, were reduced in glycerol as well as in curcumin treated rats. The results obtained in this study provided additional evidence that despite its limited antioxidant activity curcumin did not protect kidney in myoglobinuric model of ARF.
Assuntos
Injúria Renal Aguda/prevenção & controle , Antineoplásicos/farmacologia , Curcumina/farmacologia , Glicerol/toxicidade , Injúria Renal Aguda/induzido quimicamente , Administração Oral , Animais , Nitrogênio da Ureia Sanguínea , Antígenos CD13/metabolismo , Creatinina/sangue , Curcumina/administração & dosagem , Glutamil Aminopeptidase/metabolismo , Glutationa/metabolismo , Rim/efeitos dos fármacos , Rim/enzimologia , Masculino , Mioglobinúria/induzido quimicamente , Mioglobinúria/prevenção & controle , Peptídeo Hidrolases/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoAssuntos
Doenças dos Cavalos/epidemiologia , Mioglobinúria/veterinária , Pesquisa/organização & administração , Rabdomiólise/veterinária , Animais , Europa (Continente) , Doenças dos Cavalos/etiologia , Doenças dos Cavalos/prevenção & controle , Cavalos , Miocárdio/patologia , Mioglobinúria/epidemiologia , Mioglobinúria/etiologia , Mioglobinúria/prevenção & controle , Rabdomiólise/epidemiologia , Rabdomiólise/etiologia , Rabdomiólise/prevenção & controleRESUMO
Rhabdomyolysis-induced myoglobinuric acute renal failure accounts for about 10-40% of all cases of acute renal failure (ARF). Nitric oxide and reactive oxygen intermediates play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). This study was designed to investigate the effect of molsidomine and L-arginine in glycerol induced ARF in rats. Six groups of rats were employed in this study, group I served as control, group II was given 50% glycerol (8 ml/kg, intramuscularly), groups III and IV were given glycerol plus molsidomine (5 mg/kg, and 10 mg/kg p.o. route respectively) 60 min prior to the glycerol injection, group V animals were given glycerol plus L-arginine (125 mg/kg, p.o.) 60 min prior to the glycerol injection, and group VI received L-NAME (10 mg/kg, i.p.) along with glycerol 30 min prior to glycerol administration. Renal injury was assessed by measuring plasma creatinine, blood urea nitrogen, creatinine and urea clearance. The oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of catalase, reduced glutathione and superoxide dismutase. Tissue and urine nitrite levels were measured as an index of total nitric oxide levels. Glycerol treatment resulted in a marked decrease in tissue and urine nitric oxide levels, renal oxidative stress and significantly deranged the renal functions along with deterioration of renal morphology. Pre-treatment of animals with molsidomine (10 mg/kg) and L-arginine 60 min prior to glycerol injection markedly attenuated fall in nitric oxide levels, renal dysfunction, morphological alterations, reduced elevated TBARS and restored the depleted renal antioxidant enzymes. The animals treated with L-NAME along with glycerol further worsened the renal damage observed with glycerol. As a result, our results indicate that molsidomine and L-arginine may have beneficial effects in myoglobinuric ARF.
Assuntos
Injúria Renal Aguda/prevenção & controle , Arginina/farmacologia , Molsidomina/farmacologia , Mioglobinúria/prevenção & controle , Doadores de Óxido Nítrico/farmacologia , Rabdomiólise/complicações , Animais , Glicerol/toxicidade , Rim/patologia , Masculino , Óxido Nítrico/metabolismo , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
BACKGROUND: Acute renal failure (ARF) secondary to crush injury is one of the leading causes of hospitalization and death in survivors of massive disasters. The standard therapy for crush injury, intravenous (i.v.) hydration and alkalinization of urine, is often not feasible after a mass disaster; therefore, oral rehydration and urinary alkalinization may be a useful substitute. METHODS: We developed and evaluated an oral alkalinizing solution (OAS) to induce alkaline diuresis. We enrolled 12 volunteer Iranian Army recruits (mean age 19.4+/-0.8 years) who drank an average of 650 ml of OAS for 12 h. We checked the volume and pH of their urine every hour, and measured venous blood gas and electrolytes at 6, 12 and 15 h. RESULTS: All subjects tolerated the OAS without adverse events, and had active diuresis (>200 ml/h) after an average of 3.0+/-0.7 h. Their urine became alkaline (pH>7.0) within an average of 3.25+/-0.8 h. There were no significant electrolyte abnormalities. CONCLUSIONS: OAS seems to be a safe and promising means of inducing alkaline diuresis. It may be a feasible alternative to i.v. hydration to prevent ARF secondary to crush injuries in the context of mass disasters where i.v. hydration is not possible. A dose of 10 ml/kg/h may be the correct amount to induce alkaline diuresis within the first 12 h after crush injuries. The use of OAS for this purpose should be evaluated further.
Assuntos
Injúria Renal Aguda/prevenção & controle , Diuréticos , Mioglobinúria/prevenção & controle , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Diuréticos/química , Humanos , Masculino , Mioglobinúria/complicaçõesRESUMO
1. Free radicals and nitric oxide (NO) play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). The aim of the present study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an anti-oxidant, on the myoglobinuric ARF induced by intramuscular hypertonic glycerol injection. 2. Thirty rats were divided equally into three groups. Rats in group 1 were given saline and those in groups 2 and 3 were injected with glycerol (10 mL/kg, i.m.). Concomitant and 24 h after glycerol injection, CAPE (10 micromol/kg, i.p.) was administered to group 3 rats. Forty-eight hours after glycerol injection, blood samples and kidney tissues of rats were taken under anaesthesia. 3. Plasma concentrations of urea, creatinine, malondialdehyde (MDA) and NO were determined, as were superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities and MDA levels in kidney tissues. Kidney morphology was also investigated. 4. In the group receiving CAPE, although SOD enzyme activity was found to be increased, we failed to find any protective effect of CAPE on other parameters investigated. Moreover, although CAPE significantly decreased NO levels, it increased plasma concentrations of urea and MDA. 5. We suggest that the effect of CAPE in decreasing NO concentrations may further increase the renal ischaemia in this model. Thus, CAPE may have a worsening rather than beneficial effect under these conditions in this model of ARF.
Assuntos
Injúria Renal Aguda/prevenção & controle , Antioxidantes/farmacologia , Ácidos Cafeicos/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Animais , Antioxidantes/efeitos adversos , Antioxidantes/metabolismo , Ácidos Cafeicos/efeitos adversos , Glicerol , Injeções Intramusculares , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mioglobinúria/induzido quimicamente , Mioglobinúria/metabolismo , Mioglobinúria/prevenção & controle , Necrose , Óxido Nítrico/metabolismo , Álcool Feniletílico/efeitos adversos , Ratos , Ratos WistarRESUMO
BACKGROUND: Myoglobinuric acute renal failure causes increased oxidative stress. Since ethanol upregulates renal antioxidant enzymes and wine polyphenols behave as antioxidants, we tested the hypothesis that red wine components would ameliorate the renal damage caused by rhabdomyolysis. METHODS: Adult rats received water (control), alcohol-free red wine, ethanol 12.5% (v/v) or red wine for 10 weeks. Rhabdomyolysis was induced by glycerol injection (50%, 10 ml/kg, i.m.), and urine and blood samples were collected 6 h later to measure renal function parameters, creatine kinase (CK) activity, free F(2)-isoprostanes and total antioxidant capacity. Kidneys were then harvested for morphological studies and determinations of lipid peroxidation, protein carbonylation, (Na + K)-ATPase and antioxidant enzyme activities. RESULTS: In the control group, myoglobinuria was associated with a 68% decrease in creatinine clearance and increases in plasma creatinine and blood urea nitrogen of 3.2 and 1.8 times above baseline, respectively. Controls also showed increases in plasma free F(2)-isoprostanes levels and CK activity, together with enhanced renal expression of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase, as well as increased production of malondialdehyde and carbonyls. Rhabdomolysis reduced renal (Na + K)-ATPase activity and this reduction was associated with a 5-fold increase in fractional sodium excretion as well as morphological damage to the kidney. These changes were significantly attenuated by pretreatment with chronic red wine exposure prior to glycerol injection. A less marked degree of functional and biochemical protection was also observed in response to the administration of alcohol-free red wine and ethanol. CONCLUSIONS: The present data suggest that red wine protects against functional, biochemical and morphological damage caused by rhabdomyolysis in the rat, and this protection may be due to the synergistic effects of ethanol and non-alcoholic red wine components.
Assuntos
Injúria Renal Aguda/prevenção & controle , Antioxidantes/farmacologia , Etanol/farmacologia , Flavonóis/farmacologia , Vinho , Injúria Renal Aguda/etiologia , Animais , Masculino , Modelos Animais , Mioglobinúria/etiologia , Mioglobinúria/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Rabdomiólise/complicaçõesRESUMO
Oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). This study was designed to determine the protective influence of N-acetylcysteine (NAC), a hydroxyl radical scavenger, and treatment in an experimental model of myoglobinuric-ARF induced by intramuscular injection of hypertonic glycerol in rats. The rats were randomly distributed into five groups: Group 0 (n = 10), was assigned to receive 2mL saline (0,9%) intraperitoneally (ip); Group 1 (n = 10), NAC ip in a dose of 0 mg/100 g of body weight 30 min before the intramuscular (im) injection of 50% glycerol (10 mg/kg); Group 2 (n = 10), received saline 0,9% ip in a equivalent volume of NAC in Group I before the im injection of glycerol; Group 3 (n = 10), received NAC ip in a dose of 10 mg/100 g after im injection of glycerol; Group 4 (n = 10), saline 0,9% ip in a equivalent volume of NAC of the Group 3 after im administration of glycerol. After 24 h rats were sacrificed and kidney morphology and renal function were determined. A severe renal failure was produced by glycerol injection in the Groups 1, 2, 3, and 4, with significant tubular proximal necrosis and cast formation, and creatinine and urea concentrations were elevated in these groups without significant differences among groups, but Group 0 where the values were significantly lower. The results of this study suggests that ip administration of NAC in rats before or after glycerol injection do not confer protection against impairment of renal function under these conditions in this model of myoglobinuric-ARF.
Assuntos
Acetilcisteína/uso terapêutico , Injúria Renal Aguda/prevenção & controle , Sequestradores de Radicais Livres/uso terapêutico , Mioglobinúria/prevenção & controle , Acetilcisteína/administração & dosagem , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Crioprotetores/efeitos adversos , Modelos Animais de Doenças , Sequestradores de Radicais Livres/administração & dosagem , Glicerol/efeitos adversos , Soluções Hipertônicas/efeitos adversos , Injeções Intraperitoneais , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Mioglobinúria/induzido quimicamente , Mioglobinúria/patologia , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Melatonin, the pineal hormone with antioxidative properties was administered to rats with glycerol-induced myoglobinuric acute renal failure (Gly-ARF). This model is characterized by acute tubular necrosis mediated by heme-iron oxidative stress. Rats received melatonin (20 mg/kg) concomitant and 3 h after glycerol injection. Gly-ARF rats showed at 24 h a 78% reduction in glomerular filtration rate, whereas this decrement was significantly reduced to 35% in the melatonin treated Gly-ARF rats. Tubular function evaluated by tubular reabsorption of sodium and lithium was also preserved in melatonin treated rats. The histologic analysis revealed extensive cortical tubular necrosis that was significantly reduced by melatonin treatment. The renal concentration of malondialdehyde (MDA) was increased 6 h after glycerol injection in Gly-ARF and this elevation was prevented when melatonin was administered. Renal concentration of reduced glutathione (GSH) was decreased at 6 h in Gly-ARF and melatonin did not reverse this decrease. It was concluded that melatonin administration attenuated the renal injury in the glycerol model of acute renal failure and reduced kidney oxidative stress through a GSH-independent mechanism.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Antioxidantes/uso terapêutico , Crioprotetores/efeitos adversos , Glicerol/efeitos adversos , Melatonina/uso terapêutico , Mioglobinúria/induzido quimicamente , Mioglobinúria/prevenção & controle , Injúria Renal Aguda/patologia , Animais , Antioxidantes/administração & dosagem , Crioprotetores/administração & dosagem , Modelos Animais de Doenças , Esquema de Medicação , Taxa de Filtração Glomerular/efeitos dos fármacos , Glicerol/administração & dosagem , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Túbulos Renais/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Melatonina/administração & dosagem , Mioglobinúria/patologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Rhabdomyolysis may account for about 10% of all cases of acute renal failure (ARF). This study was performed to explore the protective influence of proanthocyanidins from seeds of grape in an experimental model of myoglobinuric ARF. Rats were injected with 50% glycerol (8 mL/kg, im) followed immediately and daily in the next three days by ip proanthocyanidins (20 mg/kg) or saline. After 96 h rats were sacrificed and kidney morphology, kidney cortex peptidase activities, and malondialdehyde (MDA) content were determined. A moderate renal failure was produced by glycerol injection with blood urea of 31.8+/-11.0 vs. 7.68+/-0.24 m mol/L, and serum creatinine of 153. +/-38.2 vs. 39.6+/-9.0 micromol/L, in glycerol-induced ARF vs. control rats, respectively. Rats that received proanthocyanidins in addition to glycerol had significantly lower (p < 0.01) blood urea and serum creatinine levels compared to those receiving glycerol alone. These functional differences between the glycerol and glycerol plus proanthocianidins groups were also confirmed histologically. Kidney cortex dipeptidylpeptidase IV (DPP IV) activity was not significantly changed in glycerol-induced ARF, however, markedly increased after proanthocyanidins treatment. Kidney cortex malondialdehyde content was found significantly increased in glycerol-induced ARF over control level, and was markedly reduced by proanthocyanidin treatment. Taken together, these results provide strong evidence for the protective role of proanthocyanidins from seeds of grape in glycerol-induced ARF. The effect is probably due to the antioxidant activity of proanthocyanidins and to increased expression of kidney cortex DPP IV with effective degradation of TNF-alpha. This may provide therapeutic opportunities of preventing and/or treating myoglobinuric ARF in humans.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Antocianinas/administração & dosagem , Antioxidantes/administração & dosagem , Rim/patologia , Malondialdeído/metabolismo , Proantocianidinas , Rabdomiólise/prevenção & controle , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Análise de Variância , Animais , Modelos Animais de Doenças , Flavonoides/administração & dosagem , Glicerol , Injeções Intraperitoneais , Rim/efeitos dos fármacos , Rim/metabolismo , Testes de Função Renal , Masculino , Malondialdeído/análise , Mioglobinúria/tratamento farmacológico , Mioglobinúria/prevenção & controle , Probabilidade , Ratos , Ratos Wistar , Valores de Referência , Rabdomiólise/complicações , Rabdomiólise/tratamento farmacológico , RosalesRESUMO
Renal ischemia as well as oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). On the other hand, flavonoids, a diverse group of constituents naturally occurring in plants, have a strong antioxidative activity, and have been implicated in vascular relaxation. In this study the protective effect of a new bioflavonoid proanthocyanidin-BP1 (BP1), extracted from seeds of grapes, was evaluated in glycerol-induced ARF in rats. Stereological methods were used to quantify changes in renal morphology associated with ARF. Volume density of tubular lumen and intratubular cast formations, nuclear parameters (area, diameter, volume) of epithelial cells in the cortical proximal tubules, and glomerular parameters (surface area, diameter, volume, perimeter) were estimated on kidney sections of rats treated either with 50% glycerol (8 mL/kg i.m.) alone. BP1 (20 mg/kg i.p.) in addition to glycerol, or BP1 alone. It was noted that the volume density of tubular lumen and cast formations were significantly lower (p < 0.001) in kidneys of the rats treated with BP1 in addition to glycerol, compared with those treated with glycerol alone. There were no significant differences in glomerular and nuclear parameters between glycerol treated, and BP1 in addition to glycerol treated rats. Renal function was significantly improved in rats treated with BP1 in addition to glycerol. The results suggest that BP1 is a protective agent in glycerol model of ARF. This effect is probably due to the antioxidative activity of BP1 and reduced toxicity of myoglobin in renal tissue. Moreover, it is possible that the ability of BP1 to protect the kidney is dependent upon renal vascular relaxation. The potential beneficial effects of bioflavonoid-BP1 demonstrated in experimental ARF could be considered in therapy of myoglobinuric ARF.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Antocianinas/farmacologia , Antioxidantes/farmacologia , Proantocianidinas , Animais , Flavonoides/farmacologia , Glicerol , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Mioglobinúria/induzido quimicamente , Mioglobinúria/prevenção & controle , Ratos , Ratos WistarRESUMO
Myoglobinuria secondary to myonecrosis is a proven cause of renal failure, especially in critically ill patients. Physiologic amputation or cryoamputation has been used at our institution for the past two decades as a safe and effective treatment for lower extremity infection, intractable rest pain, and irreversible myonecrosis. We retrospectively studied five critically ill patients with myonecrosis of lower extremities associated with myoglobinuria. The etiology of myonecrosis included preexisting peripheral vascular disease or crush injury to the lower extremities. It was determined that all five patients were too ill to undergo emergency amputation. Myoglobinuria was documented in all five patients and cleared within 24 hours of physiologic amputation in four patients. All five patients had elevated creatine phosphokinase levels (mean 20,270 mU/mL, range 12,090 to 43,164 mU/mL) that significantly decreased within 48 hours of physiologic amputation (mean 6,488 mU/mL, range 2,250 to 13,580 mU/mL). Mechanical ventilation and cardiovascular support were required in four patients. All patients had transient episodes of renal insufficiency with two progressing to anuric renal failure and requiring dialysis. One patient's renal failure resolved after 56 days, but the other patient died of a cerebrovascular accident 22 days after initiation of physiologic amputation. The mean duration of physiologic amputation was 15.6 days (range 5 to 32 days) with no significant complication due to physiologic amputation. All five patients had surgical amputation successfully. Three patients survived. The two deaths in the study were due to a cerebrovascular accident in one patient and a cardiopulmonary arrest in another. Physiologic amputation is a treatment option that halts myonecrosis, prevents myoglobinuria, and lessens the risk of associated acute renal failure. Physiologic amputation may be appropriately used in patients with myoglobinuria due to extremity myonecrosis who are deemed too critically ill to survive emergency amputation.
Assuntos
Injúria Renal Aguda/prevenção & controle , Amputação Cirúrgica/métodos , Criocirurgia/métodos , Traumatismos da Perna/complicações , Mioglobinúria/prevenção & controle , Doenças Vasculares Periféricas/complicações , Rabdomiólise/complicações , Ferimentos não Penetrantes/complicações , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Idoso , Amputação Cirúrgica/efeitos adversos , Amputação Cirúrgica/mortalidade , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Comorbidade , Creatina Quinase/sangue , Creatinina/sangue , Estado Terminal , Criocirurgia/efeitos adversos , Criocirurgia/mortalidade , Diabetes Mellitus/epidemiologia , Emergências , Humanos , Pessoa de Meia-Idade , Mioglobinúria/sangue , Mioglobinúria/etiologia , Mioglobinúria/urina , Terapia de Substituição Renal , Estudos Retrospectivos , Rabdomiólise/epidemiologia , Taxa de Sobrevida , Torniquetes , Resultado do TratamentoRESUMO
The interrelationships of renal cortical renin content RCRC, sodium chloride excreting and the severity of renal failure were studied in the glycerol-induced acute myohemoglobinuric renal failure model in the rat. Protocols were designed to increase sodium chloride excretion without necessarily resulting in RCRC depletion. Our data fail to demonstrate a relationship between RCRC and severity of renal failure, but they demonstrate an excellent inverse correlation between the sodium chloride excretion of the animals in the 24 h prior to glycerol administration and the severity of resulitng renal failure. The protection of long-term saline-drinking animals should properly be ascribed to the associated natriuresis which develops much before RCRC depletion during the time course of saline drinking. The exact mechanism by which natriuresis exerts its protective effect needs further elucidation, but our data argue against a major role for RCRC in the pathogenesis of acute experimental renal failure.